Higher osimertinib introduction rate achieved by multiple repeated rebiopsy after acquired resistance to first/second generation EGFR‐TKIs

Abstract

Background Indication for treatment with osimertinib after first/second generation (1/2G) epidermal growth factor receptor‐tyrosine kinase inhibitor (EGFR‐TKI) resistance depends on T790M mutation detected by rebiopsy. The aim of our study was to analyze the data on clinical practice at our hospital where histological rebiopsy is actively carried out multiple times. Methods We retrospectively reviewed our electronic medical records of EGFR‐mutant non‐small cell lung cancer (NSCLC) patients to examine clinical rebiopsy situation, T790M detection rate, osimertinib introduction rate and associated outcomes. Results Among 95 patients with EGFR‐mutant NSCLC, 72 patients received 1/2G EGFR‐TKIs. Of 60 with progressive disease on 1/2G EGFR‐TKIs, 50 (83%) underwent rebiopsy. T790M was detected in 40 (80%) of 50, resulting in a 79% osimertinib introduction rate, as one patient refused osimertinib. T790M was detected by first rebiopsy in 18 (36%) of 50 patients, and by second or subsequent rebiopsy in 22 (44%). Median time to treatment failure of T790M‐positive patients at first rebiopsy was 22.6 (95% confidence interval [CI]: 10.2–32.8) months, and those at multiple repeated rebiopsy was 20.9 (95% CI: 8.6–not reached) months (p = 0.64). Median overall survival (OS) in osimertinib introduced group was 92.5 (95% CI: 62.9–not reached), while in nonosimertinib median OS was 39.0 months (95% CI: 22.2–not reached) (p = 0.04). Conclusions T790M detection rate was increased by multiple repeated rebiopsy, achieving a higher osimertinib introduction rate. This higher introduction rate could contribute to better prognosis of EGFR‐mutant NSCLC patients.

Classification and regression tree for estimating predictive markers to detect T790M mutations after acquired resistance to first line EGFR-TKI: HOPE-002

“…CART classi ed three distinct groups of patients based on variables that were strongly associated with detecting acquired T790M mutations (age, CYF, LDH, and liver metastasis); however, the AUROC was not satisfactory. In our study, the T790M detection rates between cases with deletion 19 and L858R mutations were different, in which is consistent with a previous report [14,23,24]. Accordingly, we decided to analyze predictive markers for the detection of T790M mutations for each type of EGFR mutation.…”

“…Previous reports have shown the value of performing a re-biopsy since patients who initially present as T790M-negative exhibited T790M-positive conversion after repeated re-biopsy. In these studies, performing re-biopsies increased their T790M detection rates from 36-80% and 45-67% [14,18]. While this method increases the frequency of T790M detection, it also increases the number of invasive procedures done on patients.…”

“…Although we classi ed the three groups according to the frequency of T790M, the AUROC was found to be low. Next, we analyzed predictive markers for detecting T790M mutations with each type of EGFR mutation since a previous analysis found that its frequency varies according to EGFR type [14]. The CART identi ed three distinct groups in deletion 19 based on certain variables (albumin (Alb), LDH, bone metastasis, pleural effusion, and WBC), with an AUROC of 0.81 (95% CI: 0.71-0.91) (Figure 2b).…”

Incidental diagnosis of pulmonary cryptococcosis by rebiopsy for epidermal growth factor receptor T790M mutation: A case report

“…Since the patient had none of the above symptoms, and serum cryptococcal glucuronoxylomannan antigens were negative, it was impossible to suspect pulmonary cryptococcosis clinically. Lung cancer treatment is now very advanced, suggesting the usefulness of rebiopsy in non‐ EGFR T790M mutation‐positive cases to administer osimertinib 7 . With the current advances in cancer drug therapy, some patients present with multiple malignancies.…”

Effectiveness and Safety of EGFR-TKI Rechallenge Treatment in Elderly Patients with Advanced Non-Small-Cell Lung Cancer Harboring Drug-Sensitive EGFR Mutations

“…Currently, T790M can be detected by repeating liquid biopsy instead of tissue re-biopsy. The expression rate of T790M due to repetition of tissue re-biopsy and liquid biopsy is different depending on the report [ 35 , 36 , 37 , 38 , 39 , 40 ]. However, the expression frequency of T790M in the re-biopsy of elderly patients is unclear.…”